Continuous method for preparing carbonate esters

ABSTRACT

In one embodiment, a continuous process for preparing organic carbonate solvent of Formula (I) as described herein comprises contacting a first reactant (an alcohol) with a reactive carbonyl source (carbonyldiimidazole (CDI) or an alkylchloroformate) in the presence of a catalyst in reaction stream flowing through a continuous flow reactor at temperature 20° C. to about 160° C. and at a flow rate providing a residence time in the range of about 0.1 minute to about 24 hours; collecting a reactor effluent exiting from the continuous flow reactor; recovering a crude product from the reactor effluent; and distilling the crude product to obtain the organic carbonate compound of Formula (I). In another embodiment, the first reactant is an epoxide and the carbonyl source is carbon dioxide.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.16/812,628 filed on Mar. 9, 2020, which is incorporated herein byreference in its entirety.

CONTRACTUAL ORIGIN OF THE INVENTION

The United States Government has rights in this invention pursuant toContract No. DE-AC02-06CH11357 between the United States Government andUChicago Argonne, LLC representing Argonne National Laboratory.

FIELD OF THE INVENTION

This invention relates to a continuous method for preparing carbonateesters, which are useful, e.g., in non-aqueous solvents and electrolytesfor electrochemical cells and batteries.

BACKGROUND

Organic carbonate ester compounds have been found to be useful aselectrolyte solvents for non-aqueous electrochemical cells and batteries(e.g., lithium batteries). Numerous carbonate esters have been utilizedin rechargeable battery systems, including linear carbonates and cycliccarbonates. In some cases, conventional batch processes to prepare thecarbonate esters can be expensive and difficult to scale up.

There is an ongoing need for new methods of preparing organic carbonateesters for use, e.g., in rechargeable battery systems. The methodsdescribed herein address this ongoing need.

SUMMARY OF THE INVENTION

A continuous processes for preparing organic carbonate solvent ofFormula (I) is described herein.

In Formula (I) Z is a covalent bond; x is 0 or 1; R¹ is C₁-C₆ alkyl orC₁-C₆ fluoroalkyl bearing at least one fluoro substituent; R² is H,C₁-C₆ alkyl or C₁-C₆ fluoroalkyl bearing at least one fluorosubstituent. When x is 0, both R³ and R⁴ are CH₂ and are not directlybonded together. When x is 1, R³ and R⁴ both are CH, R² is H, and R³ andR⁴ are directly connected by a covalent bond.

The process described herein involves contacting an alcohol or anepoxide with a reactive carbonyl source (e.g., an alkyl chloroformate, afluoroalkyl chloroformate, carbonyldiimidazole (CDI), or carbon dioxide)in the presence of a catalyst in a continuous flow reactor at atemperature in the range of about 20° C. to about 160° C. Typically, thealcohol or epoxide is dissolved in an aprotic solvent e.g., at aconcentration of about 0.5 to 6 M, and the catalyst and carbonyl sourceare dissolved in the same solvent. Typical residence times for theprocesses described herein are about 0.1 minute to about 24 hours,depending on the internal volume of the reactor, the temperature,solvent, catalyst, the other reactants, and the like. In practice, thereaction stream is pumped through the heated reactor at temperature,flow rate, and residence time sufficient to achieve a desired level ofconversion of the alcohol or epoxide to the compound of Formula (I),e.g., complete or maximal conversion. Optionally, any remaining carbonylsource is quenched before recovering a crude product from a reactoreffluent flowing out of the reactor. The crude product is then purified,e.g., by distillation to obtain the organic carbonate compound ofFormula (I). Scheme 1 illustrates three embodiments (A, B, and C) of theprocess.

Scheme 1, A, illustrates a process wherein an alcohol of Formula (II) isreacted with an alkyl chloroformate or fluoroalkyl chloroformate as thecarbonyl source, wherein R and R′ are independently C₁-C₆ alkyl or C₁-C₆fluoroalkyl bearing at least one fluoro substituent. Scheme 1, B,illustrates a process wherein the alcohol of Formula (II) is reactedwith carbonyldiimidazole (CDI) as the carbonyl source (i.e., X(CO)X inwhich X is N-imidazolyl). Scheme 1, C, illustrates a process wherein anepoxide of Formula (III) is reacted with carbon dioxide as the carbonylsource.

Formula (Ia) in Scheme 1 corresponds to the organic carbonate of Formula(I) wherein x is 0 (i.e., a linear carbonate ester); R² and R³ both areCH₂; R of Formula (Ia) corresponds to R of Formula (I); and R of Formula(Ia) corresponds to R² of Formula (I).

Formula (Ib) in Scheme 1 corresponds to the organic carbonate of Formula(I) wherein x is 0; R³ and R⁴ both are CH₂; and the two R groups ofFormula (Ib) correspond to R¹ and R² of Formula (I).

Formula (Ic) in Scheme 1 corresponds to the organic carbonate of Formula(I) wherein x is 1 (i.e., a cyclic carbonate ester), R³ and R⁴ both areCH; R² is H; and R of Formula (Ic) corresponds to R¹ of Formula (I).

The solvents utilized in the processes shown in Scheme 1 are aproticsolvents, preferably polar aprotic solvents, such as, for example,nitriles (e.g., acetonitrile), ethylene glycol ethers (e.g., glyme,diglyme, butyl methyl diethylene glycol ether, butyl methyl triethyleneglycol ether), ketones (e.g., acetone or methylisopropylketone (MIK)),amides (e.g., dimethylformamide (DMF) or N-methylpyrrolidone (NMP)),organic carbonates (e.g., dimethyl carbonate (DMC) or diethyl carbonate(DEC)), phosphoramides (e.g., hexamethylphosphoramide (HMPA), othersubstituted phosphoramides, etc.), and the like.

The catalysts utilized in the processes shown in Scheme 1 comprise, forexample, organic nitrogen-containing bases, organicphosphorus-compounds, and the like, such as, e.g., tertiary amines(e.g., diisopropylethylamine (DIPEA)); bicyclic amidines (e.g.,1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)); phosphazenes (e.g.,2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine(BEMP)); bicyclic guanidines (e.g., 1,5,7-triazabicyclo[4.4.0]dec-5-ene(TBD)); quaternary ammonium salts (e.g., tetraalkylammonium halides,N-alkylated heterocycle salts, such as N-alkylpyridinium halides);quaternary phosphonium salts (e.g., methyltriphenylphosphonium bromide);acid addition salts of organic nitrogen-containing bases (e.g.,hydrochloride salts, hydrobromide salts, hydroiodide salts, or organicacid salts of tertiary amines, amidines, guanidines, phosphazenes,nitrogen-heterocycles, and the like); and ionic liquids comprising ionsof such catalysts.

The following non-limiting embodiments of the methods described hereinare provided below to illustrate certain aspects and features of thepresent invention.

Embodiment 1 is a continuous processes for preparing organic carbonatesolvent of Formula (I):

comprising the steps of:

(a) contacting a first reactant with a reactive carbonyl source inreaction stream containing a catalyst flowing through a continuous flowreactor at a temperature in the range of about 20° C. to about 160° C.,and at a flow rate providing a residence time in the range of about 0.1minute to about 24 hours;

(b) optionally quenching any remaining reactive carbonyl source;

(c) collecting a reactor effluent exiting from the continuous flowreactor;

(d) recovering a crude product from the reactor effluent; and

(e) purifying the crude product to obtain the organic carbonate compoundof Formula (I);

wherein:

the reactive carbonyl source is selected from the group consisting of achloroformate of formula Cl(CO)OCH₂R′, carbonyldiimidazole (CDI), andcarbon dioxide;

when the carbonyl source is the chloroformate or CDI the first reactantis an alcohol of Formula (II):

when the carbonyl source is carbon dioxide the first reactant is anepoxide of Formula (III):

the catalyst comprises at least one material selected from the groupconsisting of a tertiary amine, a bicyclic amidine, a phosphazene, abicyclic guanidine, a quaternary ammonium salt, a quaternary phosphoniumsalt, an acid addition salt of a tertiary amine, an acid addition saltof a bicyclic amidine, an acid addition salt of a phosphazene, an acidaddition salt of a bicyclic guanidine; an acid addition salt of anitrogen-heterocycle, and an ionic liquid comprising an ion of one ormore of the foregoing catalysts;

Z is a covalent bond;

x is 0 or 1;

R¹ is C₁-C₆ alkyl or C₁-C₆ fluoroalkyl bearing at least one fluorosubstituent;

R² is H, C₁-C₆ alkyl or C₁-C₆ fluoroalkyl bearing at least one fluorosubstituent;

when x is 0, both R³ and R⁴ are CH₂ and are not directly bondedtogether;

when x is 1, R³ and R⁴ both are CH, R¹ is H, and R³ and R⁴ are directlyconnected by a covalent bond; and

R and R′ independently are C₁-C₆ alkyl or C₁-C₆ fluoroalkyl comprisingat least one fluoro substituent.

Embodiment 2 is the process of embodiment 1, wherein the reaction streamfurther comprises an aprotic organic solvent in which the firstreactant, the carbonyl source, and the catalyst are dissolved; andpreferably the alcohol or epoxide is dissolved in the solvent at aconcentration of about 0.5 to about 6 molar (M).

Embodiment 3 is the process of embodiment 1 or 2, wherein the aproticorganic solvent comprises at least one material selected from the groupconsisting of an ether, a nitrile, an ester, an organic carbonate ester,an amide, a ketone, a sulfone, a sulfoxide, a hydrocarbon, a halogenatedhydrocarbon, a phosphoramide, and an ionic liquid.

Embodiment 4 is the process of any one of embodiments 1 to 3, whereineach of R¹ and R² independently is C₁ to C₄ alkyl or C₁ to C₄fluoroalkyl.

Embodiment 5 is the process of any one of embodiments 1 to 4, whereinthe compound of Formula (I) is purified in step (e) by distillation.

Embodiment 6 is the process of any one of embodiments 1 to 5, whereinthe first reactant is the alcohol of Formula (II), the carbonyl sourceis the chloroformate of formula Cl(CO)OCH₂R′; the catalyst is selectedfrom the group consisting of a tertiary amine, an aromatic nitrogenheterocycle, and a quaternary ammonium hydroxide; the catalyst ispresent in the reaction stream at a concentration of about 100 to 150mol % relative to the alcohol; and the reaction stream comprises anaprotic organic solvent selected from the group consisting of a nitrile,a glycol ether, and ketone in which the alcohol, the chloroformate andthe catalyst are dissolved.

Embodiment 7 is the process of embodiment 6, wherein the alcohol isdissolved in the solvent at a concentration of about 0.5 to about 6molar (M).

Embodiment 8 is the process of embodiment 6, wherein the solventcomprises acetonitrile.

Embodiment 9 is the process of embodiment 6, wherein the catalystcomprises diisopropylethylamine.

Embodiment 10 is the process of embodiment 9, wherein the alcohol is2,2,2-trifluoroethanol; the carbonyl source is methylchloroformate; thecatalyst is diisopropylethylamine; the solvent is acetonitrile; thealcohol is dissolved in the solvent at a concentration of about 0.5 to 6M; and the continuous flow reactor is heated at a temperature in therange of about 30° C. to about 110° C.

Embodiment 11 is the process of any one of embodiments 1 to 5, whereinthe first reactant is the alcohol of Formula (II); the carbonyl sourceis the CDI; the catalyst is selected from the group consisting tertiaryamine, an aromatic nitrogen heterocycle, and a quaternary ammoniumhydroxide; the catalyst is present in the reaction stream at aconcentration of about 2 to 15 mol % relative to the alcohol; and thereaction stream comprises an aprotic organic solvent selected from thegroup consisting of a nitrile, an ester, an organic carbonate ester, anamide, a ketone, a sulfone, a sulfoxide, a halogenated hydrocarbon, aphosphoramide, and an ionic liquid, in which the alcohol, the CDI, andthe catalyst are dissolved; and preferably the alcohol is dissolved inthe solvent at a concentration of about 0.5 to about 6 molar (M).

Embodiment 12 is the process of embodiment 11, wherein the alcohol is2,2,2-trifluoroethanol.

Embodiment 13 is the process of embodiment 11, wherein the solventcomprises dimethylformamide.

Embodiment 14 is the process of embodiment 11, wherein the alcohol ispresent in the reaction stream in a respective molar ratio ofalcohol-to-CDI of about 1.8:1 to about 2.6:1.

Embodiment 15 is the process of embodiment 11, wherein the alcohol is2,2,2-trifluoroethanol; the solvent is selected from the groupconsisting of dimethylformamide, acetonitrile, acetone, anddimethylsulfoxide; the alcohol is present in the reaction stream in arespective molar ratio of alcohol to CDI of about 2:1 to about 3:1; andthe continuous flow reactor is heated at a temperature in the range ofabout 50 to about 120° C.

Embodiment 16 is the process of any one of embodiments 1 to 5, whereinthe first reactant is the epoxide of Formula (III); the carbonyl sourceis carbon dioxide; the catalyst is selected from the group consisting ofan acid addition salt of a bicyclic amidine, an acid addition salt of aphosphazene, an acid addition salt of a bicyclic guanidine, a quaternaryammonium halide, and a quaternary phosphonium halide; the catalyst ispresent in the reaction stream at a concentration of about 1 to 20 mol %relative to the epoxide; the carbon dioxide is present in the reactionstream at a pressure in the range of about 1 to about 10 bar; and thereaction stream comprises an aprotic organic solvent selected from thegroup consisting of a nitrile, an ester, an organic carbonate ester, anamide, a ketone, a sulfone, a sulfoxide, and a halogenated hydrocarbon;and preferably, the epoxide is dissolved in the solvent at aconcentration of about 0.5 to about 6 molar (M).

Embodiment 17 is the process of embodiment 16, wherein the reactionstream flowing through the continuous flow reactor is heated at atemperature in the range of about 50° C. to about 120° C.

Embodiment 18 is the process of embodiment 16, wherein the solventcomprises acetonitrile.

Embodiment 19 is the process of embodiment 16, wherein the epoxidecomprises 3,3,3,-trifluoropropylene-1,2-oxide.

Embodiment 20 is the process of embodiment 19, wherein the solvent isacetonitrile; the catalyst is selected from the group consisting oftetrabutylammonium bromide, tetrabutylammonium chloride,tetrabutylammonium iodide, and benzyltriethylammonium bromide; thecatalyst is present at a concentration of about 1 to about 15 mol %relative to the epoxide; and the continuous flow reactor is heated at atemperature in the range of about 50° C. to about 120° C.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 schematically illustrates a continuous flow reactor system.

FIG. 2 provides graphs of reaction yield (as determined by gaschromatography (GC)) for the different solvent and base catalystcombinations for reaction of 2,2,2-trifluoroethanol with methylchloroformate.

FIG. 3 provides a graph of conversion versus residence time andtemperature for reaction of 2,2,2-trifluoroethanol with DCI.

FIG. 4 provides a graph of conversion versus temperature and number ofequivalents of 2,2,2-trifluoroethanol relative to CDI for reaction of2,2,2-trifluoroethanol with DCI.

FIG. 5 provides a graph of conversion versus different DBU-basedcatalysts for reaction of 3,3,3-trifluoroproylene oxide with carbondioxide in acetonitrile solvent.

FIG. 6 provides a graph of conversion versus differenttetrabutylammonium (TBA)-based catalysts for reaction of3,3,3-trifluoropropylene oxide with carbon dioxide in acetonitrilesolvent.

FIG. 7 provides a graph of conversion versus different solvents forreaction of 3,3,3-trifluoropropylene oxide with carbon dioxide inacetonitrile solvent with tetrabutylammonium bromide (TBAB) catalyst.

FIG. 8 provides graphs of conversion versus residence time for differentcatalysts for reaction of 3,3,3-trifluoropropylene oxide with carbondioxide in acetonitrile solvent.

DETAILED DESCRIPTION

In one aspect, a continuous process for preparing a linear organiccarbonate solvent of Formula (I) (i.e., wherein x is 0) is described.The process comprises contacting an oxygen-containing reactant (i.e., analcohol in this aspect) with a reactive carbonyl source(carbonyldiimidazole (CDI) or a chloroformate) in the presence of acatalyst in reaction stream flowing through a continuous flow reactor ata temperature of about 20° C. to about 160° C. Typically the reactionstream is pumped through the reactor at a flow rate providing aresidence time of about 1 minute to about 24 hours. A reactor effluentcontaining the product compound of Formula (I) is collected as theeffluent exits the continuous flow reactor. The crude product isrecovered from the reactor effluent (e.g., by evaporation of solvent,precipitation extraction or any other expedient method. Purifiedcarbonate ester of Formula (I), wherein x is 0, is obtained bydistilling the crude product. In another aspect, the oxygen-containingreactant is an epoxide, the carbonyl source is carbon dioxide, and theproduct is a compound of Formula (I) wherein x is 1 (i.e., a cycliccarbonate).

In one embodiment (see Scheme 1, A), a continuous process for preparingan organic carbonate of Formula (Ia) is provided, wherein R is C₁-C₆alkyl (e.g., methyl, ethyl, propyl, isopropyl) or C₁-C₆ fluoroalkylcomprising at least one fluoro substituent (e.g., CF₃, FCH₂, CF₃CH₂,CF₃CH₂CH₂, CF₃CF₂, CF₃CF₂CF₂, and the like); and R′ is C₁-C₆ alkyl(e.g., methyl, ethyl, propyl, isopropyl, butyl) or C₁-C₆ fluoroalkylcomprising at least one fluoro substituent (e.g., CF₃, FCH₂, CF₃CH₂,CF₃CH₂CH₂, CF₃CF₂, CF₃CF₂CF₂, and the like). The method comprisescontacting an alcohol of Formula (II) as described herein with achloroformate compound (Cl—(CO)—OR′, wherein R′ is C₁-C₆ alkyl (e.g.,methyl, ethyl, propyl, isopropyl) or C₁-C₆ fluoroalkyl comprising atleast one fluoro substituent) in the presence of a catalyst in areaction stream flowing through a continuous flow reactor heated at atemperature in the range of about 20° C. to about 160° C., at a flowrate providing a residence time of about 1 minute to about 24 hours;quenching any remaining chloroformate compound; collecting an effluentstream exiting from the continuous flow reactor; recovering a crudeproduct from the so-collected effluent stream; and distilling the crudeproduct to obtain the compound of Formula (Ia). The catalyst preferablycomprises a tertiary amine such as trimethylamine, triethylamine,tributylamine, diisopropylethylamine, and the like. The catalysttypically is utilized at a concentration relative to the alcohol ofabout 100 to about 150 mol % (i.e., a molar percentage based on themolar concentration of the alcohol). In preferred embodiments thereaction stream comprises an aprotic organic solvent such asacetonitrile, acetone, dimethylformamide, dimethylsulfoxide, and thelike. Typically, the alcohol and the chloroformate are dissolved insolvent in the reaction stream at concentrations ranging from about 0.5to about 6 M. Optionally, the reaction can be performed neat (i.e., withno solvent).

In another embodiment (see Scheme 1, B), a continuous process forpreparing a compound of Formula (Ib) is provided wherein R is C₁-C₆alkyl (e.g., methyl, ethyl, propyl, isopropyl, butyl, pentyl, etc.) orC₁-C₆ fluoroalkyl comprising at least one fluoro substituent (e.g., CF₃,FCH₂, CF₃CH₂, CF₃CH₂CH₂, perfluoroethyl, perfluoropropyl,perfluorobutyl, perfluoropentyl, etc.). The method comprises contactingan alcohol of Formula (II) as described herein with carbonyldiimidazole(CDI) in the presence of a catalyst in a reaction stream flowing througha continuous flow reactor heated at a temperature of about 20° C. toabout 160° C., and a flow rate providing a residence time of about 1minute to about 24 hours; quenching any remaining CDI; collecting aneffluent stream exiting from the continuous flow reactor;

recovering a crude product from the so-collected effluent stream; anddistilling the crude product to obtain the compound of Formula (Ib). Thecatalyst preferably comprises a tertiary amine, such as trimethylamine,triethylamine, tributylamine, diisopropylethylamine, and the like. Thecatalyst typically is utilized at a concentration relative to thealcohol of about 1 to about 10 mol %. In preferred embodiments thereaction stream comprises an aprotic organic solvent such asacetonitrile, acetone, dimethylformamide, dimethylsulfoxide, and thelike. In some embodiments, at least about two equivalents of the alcoholare contacted with the CDI.

Typically, the alcohol is dissolved in solvent in the reaction stream ata concentration of about 0.5 to about 6 M, and the concentration of thealcohol in the reaction stream is at least twice the concentration ofthe CDI. Optionally, the reaction can be performed neat (i.e., with nosolvent).

In yet another embodiment (see Scheme 1, C), a continuous process forpreparing a compound of Formula (Ic) is provided wherein R is C₁-C₆alkyl (e.g., methyl, ethyl, propyl, isopropyl, butyl, pentyl, etc.) orC₁-C₆ fluoroalkyl comprising at least one fluoro substituent (e.g., CF₃,FCH₂, CF₃CH₂, CF₃CH₂CH₂, perfluoroethyl, perfluoropropyl,perfluorobutyl, perfluoropentyl, etc.). The method comprises contactingan epoxide of Formula (III) as described herein with carbon dioxide at apressure in the range of about 1 to about 10 bar in in the presence of acatalyst in a reaction stream flowing through a continuous flow reactorheated at a temperature in the range of about 50° C. to about 120° C.and a flow rate providing a residence time in the range of about 1minute to about 24 hours; collecting an effluent stream exiting from thecontinuous flow reactor; recovering a crude product from theso-collected effluent stream; and distilling the crude product to obtainthe compound of Formula (Ic). The catalyst preferably comprises aquaternary ammonium halide salt, such as tetrabutylammonium bromide(TBAB), or an N-alkylated aromatic nitrogen heterocycle. The catalysttypically is utilized at a concentration relative to the epoxide ofabout 5 to about 20 mol %. In some embodiments the reaction streamcomprises an aprotic organic solvent such as acetonitrile, acetone,dimethylformamide, and the like. Typically, the epoxide is dissolved ina solvent in the reaction stream at a concentration of about 0.5 toabout 6 M. Optionally, the reaction can be performed neat (i.e., with nosolvent).

In some embodiments, a continuous process for manufacturing a compoundof Formula (I) wherein x is 0 involves simultaneously pumping a firstsolution comprising the alcohol of Formula (II) and the catalyst in afirst aprotic solvent, and a second solution of the activated carbonylcompound (e.g., CDI, the chloroformate) in a second aprotic solvent(which can be the same or different from the first aprotic solvent)together in a continuous flow-reactor vessel heated at a temperature inthe range of about 20° C. to about 160° C., where the first and secondsolutions mix together to form a reaction stream. The reaction streamflows through the heated reactor vessel, optionally with in-line activeor static mixing, and an effluent comprising the compound of Formula (I)flows out of the vessel and is collected. Solvents are then removed fromthe effluent (e.g., by evaporation or washing with an aqueous solvent)and the resulting crude product of Formula (I) is isolated and purified,e.g., by distillation.

In another embodiment, a continuous process for manufacturing a compoundof Formula (I) wherein x is 1 involves pumping a reaction streamcomprising the epoxide of Formula (III) (either neat or dissolved in anaprotic solvent) and the catalyst through a continuous flow-reactorvessel heated at a temperature in the range of about 20° C. to about160° C., and simultaneously introducing carbon dioxide into the reactionstream (e.g., at a pressure of about 1 to about 10 bar). The reactionstream flows through the heated reactor vessel, optionally with in-lineactive or static mixing, and an effluent comprising the compound ofFormula (I) flows out of the vessel and is collected. Any solvent isremoved from the effluent (e.g., by evaporation or washing with anaqueous solvent), and the resulting crude product of Formula (I) isisolated and purified (e.g., by distillation). In some embodiments, thecarbon dioxide is introduced into the reaction stream by a mass flowcontroller and standard in-line mixer.

The heated continuous flow reactor vessel typically is either a glassmicro-reactor or a tube (e.g., a coil of tubing) within a heatingchamber (e.g., a furnace or heating bath, or a tube that includes one ofmore heating elements (e.g., heating tape) in contact with the tube.Preferably, the reaction stream has a residence time of about 1 minuteto about 24 hours within the heated reactor vessel. The vessel includesan opening (e.g., the other end of the tube from where the solution arebeing pumped) that allows the effluent stream to exit the heated vesselfor collection. As the solution or solutions are continuously pumpedinto and through the vessel, the effluent containing the productcontinuously flows out of the vessel for collection.

Typical residence times for the processes described herein are in therange of about 0.1 minute to about 24 hours. Residence time (RT) isdependent on the flow rate (Q) and the volume of the reactor (V), i.e.,RT=V/Q. The desired temperature, flow rate and residence time, areselected, at least in part, based on the reactor volume, the desiredmanufacturing throughput, and the desired level of conversion of alcoholor epoxide to the compound of Formula (I). Typically the concentrations,relative amounts, and the chemical reactivity of reagents (e.g.,alcohol, epoxide, and carbonyl source, catalyst), as well as the choiceof solvent will be taken into account when choosing operating parametersfor the flow reactor, as is well known for other types of chemicalreactions. For extremely long reactor coils/large volumes, the RT can bequite long, even though the flow rate or throughput is good. Inaddition, the internal volume of solvent present in the reactor prior topumping through the reactants (the void volume) must be displaced by thereaction stream before product effluent is collected. This can take along time before product-containing effluent is collected, but thencollection can be achieved at a good rate.

The temperature and residence time within a heated portion of thereactor are selected so that the reaction is substantially complete orat a maximum conversion by the time the effluent flows out of the heatedportion of the reactor. For a given combination of carbonyl source andalcohol or epoxide, the catalyst, solvent, reactor temperature, flowrate, and residence time can be determined by routine processdevelopment principals and screening experiments which are well known inthe chemical process art. The completeness of the reaction (conversion)can be monitored by, e.g., by gas chromatography, liquid chromatography,or thin-layer chromatography to determine when the alcohol, epoxide, thecarbonyl source, or any combination thereof, are no longer detected, orwhen production of the product compound of Formula (I) has reached amaximum. At least some byproducts of the reaction (e.g., imidazole)typically are removed from the effluent by washing with a suitablesolvent (e.g., an aqueous solvent), which also can remove some or mostof the reaction solvent (e.g., if the reaction solvent is water-solubleor water-miscible). The resulting crude carbonate ester of Formula (I)can then be purified, e.g., by distillation.

FIG. 1 schematically illustrates continuous flow reactor system 100,which comprises a coiled tubular reactor vessel housed within a heatablechamber 104 defined by a housing 106. Chamber 104 is heated by heatingunit 108 operably connected with chamber 104. In use, a first solution110 comprising a first reactant dissolved in a first solvent is pumpedinto reactor vessel 102 by pump 118 from first reservoir 114, while asecond solution 112 comprising a second reactant dissolved in a secondsolvent is pumped into reactor vessel 102 by pump 120 from secondreservoir 116, and the chamber 104 is heated at a desired temperaturevalue by heating unit 108. First solution 110 and second solution 112are mixed together at junction 122 as the solutions enter the reactorvessel 102. The combined solutions form a reaction stream that flowsthrough vessel 102 and exits reactor vessel 102 through effluent line124, and through valve 126 into either first collection vessel 130 orsecond collection vessel 132, depending on the position of a binaryvalve line 128 within valve 126. In practice, vessel 102 typically isprefilled with a solvent which is heated to the desired temperature, andthe reaction stream displaces the prefilled solvent. In such cases,first collection vessel 130 is utilized to collect the prefill solventeffluent 134. Once the volume of prefill solvent has been displaced,valve 126 can be adjusted to direct effluent 136 comprising a reactionproduct into second collection vessel 132. The arrow heads in FIG. 1indicate the direction of flow for the solutions, and effluent stream.

Non-limiting examples of suitable continuous flow reactors for use inthe methods described herein include CORNING ADVANCED-FLOW reactors(also known as CORNING AFR reactors). According to the manufacturer,Corning Inc. (Corning, N.Y.), the CORNING AFR series of reactors areavailable in models that accommodate flow rates in the range of 2 to 10mL/min (laboratory scale) up to 1000 to 8000 mL/min (the model G4 SiCreactor). Examples of such reactors are described, e.g., inInternational Patent Publication No. WO 2016/201211 to Gremetz et al.,which is incorporated herein by reference in its entirety. Otherexamples of flow reactors include the flow reactors from Syrris Ltd.,Royston, UK, such as the ASIA brand of reactors, and other lab scalereactors.

The catalysts utilized in the processes shown in Scheme 1 comprise,e.g., tertiary amines; bicyclic amidines, phosphazenes, bicyclicguanidines, quaternary ammonium salts (e.g., tetraalkylammonium halidessuch as tetrabutylammonium bromide, and N-alkylated heterocycle saltssuch as N-alkylpyridinium halides), quaternary phosphonium salts, acidaddition salts of organic nitrogen-containing bases (e.g., hydrochloridesalts, hydrobromide salts, hydroiodide salts, or organic acid salts oftertiary amines, amidines, guanidines, phosphazenes,nitrogen-heterocycles, and the like), and ionic liquids containing ionsof such materials.

Non-limiting examples of tertiary amine catalysts include, e.g.,diisopropylethylamine (DIPEA), triethylamine (TEA), tributylamine (TBA).Non-limiting examples of quaternary ammonium catalysts include, e.g.,tetrabutylammonium halides (e.g., a chloride, bromide, or iodide salt),tetraethylammonium halides, N-alkylpyridinium halides, and N-alkyl-DBUhalides. Non-limiting examples of quaternary phosphonium catalystsinclude, e.g., methyltriphenylphosphonium halides (e.g., a chloride,bromide, or iodide salt). Non-limiting examples of bicyclic amidinecatalysts include, e.g., 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU),1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,5-diazabicyclo[4.4.0]dec-5-ene(DBD), and the like. Non-limiting examples of bicyclic guanidinecatalysts include, e.g., 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD),7-methyl-1,5,7-triazabicyclo-[4.4.0]dec-5-ene (MTBD),7-ethyl-1,5,7-triazabicyclo-[4.4.0]dec-5-ene (ETBD),7-isopropyl-1,5,7-triazabicyclo-[4.4.0]dec-5-ene (ITBD), and the like.Non-limiting examples of phosphazene catalysts include, e.g.,2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine(BEMP),1-tert-butyl-4,4,4-tris-(dimethylamino)-2,2-bis[tris(dimethylamino)-phosphoranylidenamino]-2λ⁵,4λ⁵-catenadi(phosphazene)(P₄-t-Bu), and the like. Non-limiting examples of acid addition salts oforganic nitrogen-containing bases include, e.g., hydrochloride salts,hydrobromide salts, hydroiodide salts, and organic acid addition saltsof tertiary amines, amidines, guanidines, phosphazenes,nitrogen-heterocycles, and the like, such as tributylamine hydrobromide,diisopropylethylamine hydrobromide, and DBU hydrobromide. In someembodiments, two or more of the catalysts can be used together.

Solvents that are useful in the methods described herein are aproticorganic solvents, such as ethers, nitriles, esters, organic carbonates,amides, ketones, sulfones, sulfoxides, phosphoramides, hydrocarbons, andhalogenated hydrocarbons. In some embodiments, polar aprotic solventsare preferred (e.g., acetonitrile, N,N-dimethylformamide (DMF),sulfolane, dimethylsulfoxide, and the like).

Non-limiting examples of suitable ether solvents include diethyl ether,THF, 1,3-dioxolane, dioxane, and alkylene glycol ethers such asdimethoxyethane (DME or glyme), bis(2-methoxyethyl) ether (diglyme),diethylene glycol butyl methyl ether (MeO-DEG-OBu), and triethyleneglycol butyl methyl ether (MeO-TEG-OBu). Non-limiting examples ofsuitable nitrile solvents include acetonitrile, propionitrile,butyronitrile, and the like. Non-limiting examples of suitable estersolvents include methyl acetate, ethyl acetate, propyl acetate, isobutylacetate, ethyl butyrate, methyl propionate, and the like. Non-limitingexamples of suitable organic carbonate solvents include ethylenecarbonate (EC), propylene carbonate (PC), dimethyl carbonate, ethylmethyl carbonate, and the like. Non-limiting examples of suitable amidesolvents include DMF, N,N-dimethylacetamide (DMAc), N-methylpyrrolidone(NMP), and the like. Non-limiting examples of suitable ketone solventsinclude acetone, methyl ethyl ketone (MEK), and the like. Non-limitingexamples of suitable sulfone solvents include dimethylsulfone,sulfolane, and the like. A non-limiting example of a suitable sulfoxidesolvents is dimethylsulfoxide. Non-limiting examples of suitablehydrocarbon solvents include aromatic hydrocarbons such as benzene,toluene, xylenes, and the like, as well as aliphatic hydrocarbons suchas pentane, hexane, and the like. Non-limiting examples of suitablehalogenated hydrocarbon solvents include aliphatic halogenatedhydrocarbons such as dichloromethane (methylene chloride,trichloromethane (chloroform), hexachloroethane (perchloroethane),perfluoroalkanes, and the like; and aromatic halogenated hydrocarbonssuch as o-dichlorobenzene, m-dichlorobenzene, p-dichlorobenzene,1,2,3-trichlorobenzene, 1,3,5-trichlorobenzene, 1,2,4-trichlorobenzene,hexachlorobenzene, 1-chloro-3-nitrobenzene, 1-bromo-4-chlorobenzene, andthe like.

Ionic liquids, which are well known in the chemical arts, are commonlyused as alternatives to organic solvents in many chemical reactions. Inthe present processes, ionic liquids comprising ions of the variouscatalysts described herein can be used as a solvent, a catalyst, orboth. For example, ionic liquids comprising quaternary ammonium cationswith a variety of different anions, e.g., tetraalkylammonium salts, andN-alkylated nitrogen-containing aromatic heterocyclic salts (e.g.,N-alkylpyridinium salts, N,N-dialkylimidazolium salts, and the like) arewell known in the ionic liquid art as solvents for organic synthesis(see, generally Ionic Liquids in Synthesis, Peter Wasserscheid and TomWelton, Eds., WILEY-VHC Verlag GmbH & Co. KGaA, Weinheim, Germany(2007), which is incorporated herein by reference in its entirety;Chapter 2, pp. 7-55 thereof describes the synthesis of ionic liquids andvarious ionic liquid structures).

As used in reference to the methods described herein, the term“solution” refers to liquid compositions in which a material isdissolved in a solvent, as well as to liquid suspensions in whichinclude a solid material suspended in a liquid vehicle. In suchsuspensions, the solid material may be partially or completely insolublein the liquid vehicle such as an aprotic organic solvent or an ionicliquid.

As used herein, the term “alkyl” and grammatical variations thereofrefers to a univalent saturated hydrocarbon group, i.e., saturatedhydrocarbon lacking one hydrogen atom, e.g. methyl, ethyl, propyl,isopropyl, butyl, 1-methyl-1-propyl (also known as sec-butyl),2-methyl-1-propyl (also known as isobutyl), pentyl, hexyl, cyclopenyl,cyclohexyl, and the like. Alkyl groups can include linear chains ofcarbons atoms (linear alkyl), branched chains of carbon atoms (branchedalkyl), rings of carbon atoms (e.g., cycloalkyl), or any combinationthereof. In some embodiments of the compounds of Formula (I), (II) and(III) an alkyl group can comprise 1 to 6 carbon atoms (also referred toas “C₁ to C₆ alkyl”), such as methyl, ethyl, propyl, and the like. Insome embodiments, preferred alkyl groups include methyl and ethyl.Similarly, the term “fluoroalkyl” refers to an alkyl group, as describedabove, which includes at least one F substituent in place of a hydrogenthereof. The term “perfluoroalkyl” refers to an alkyl group, asdescribed above, in which all of the hydrogens thereof are replaced byF.

As used herein the term “alkylene” refers to a bivalent saturatedaliphatic radical (e.g., such as ethylene (—CH₂CH₂—), propylene(—CH₂CH₂CH₂—), and the like), which is formally regarded as derived froman alkene by opening of the double bond or from an alkane by removal oftwo hydrogen atoms from different carbon atoms. For example, an alkylenegroup can comprise 1 to 6 carbon atoms (also referred to as “C₁ to C₆alkylene”), such as methylene (—CH₂—), ethylene (—CH₂CH₂—), linearpropylene (e.g., —CH₂CH₂CH₂—), branched propylene (e.g., —CH₂(CH₃)CH₂—),and the like. As used herein, “alkylene glycol” refers to an ethylene oralkyl-substituted ethylene group bearing two hydroxyl substituents onthe adjacent carbons of the ethylene moiety, as well as to oligomers ofethylene glycol and alkyl-substituted ethylene glycols, that have twoterminal hydroxyl groups. The term “diethylene glycol” (DEG) refers toHO—CH₂CH₂—O—CH₂CH₂—OH, and “triethylene glycol” (TEG) refers toHO—CH₂CH₂—O—CH₂CH₂—O—CH₂CH₂—OH.

The following non-limiting Examples are provided to illustrate certainfeatures of the compositions and methods described herein.

Example 1. Solvent and Catalyst Evaluation for Reaction of2,2,2-Trifluoroethanol with Methyl Chloroformate

Batch reaction solubility experiments were performed with a series ofsolvents and bases for the reaction of 2,2,2-trifluoroethanol (72 μL)with methyl chloroformate (94 μL, 1.2 eq), using 1.1 mol equivalents ofbases and 1.0 ml of solvent. Table 1 provides results for the solubilityof the reaction mixture/product for the different catalyst(triethylamine (TEA), diisopropylethylamine (DIPEA), and Pyridine (Pyr))and solvent (dichloromethane (DCM), dimethylformamide (DMF), dibutylethylene glycol ether (EG(OBu)₂), sulfolane, and acetonitrile (MeCN)combinations, where “insol” means a precipitate was observed; “sol”means no precipitate was observed, and “sol/2 phase” means there was noprecipitate, but two phases were observed.

TABLE 1 TEA DIPEA Pyr DCM insol sol sol DMF insol sol sol EG(OBu)₂ insolsol/2 phase insol Sulfolane insol sol/2 phase sol MeCN insol sol sol

Additional reaction solubility experiments were set up with a series ofsolvents and bases for the reaction of 2,2,2-trifluoroethanol (0.29 mL)with methyl chloroformate (0.37 mL, 1.1 eq), using 1.1 mol equivalentsof base and 1.0 ml of solvent. Table 2 provides solubility screeningresults for the different catalyst (DIPEA, tributylamine (TBA),N-methylmorpholine (NMN), and imidazole (Imid)) and solvent (acetone,MeCN, butyl methyl diethylene glycol (MeO-DEG-OBu) and butyl methyltriethylene glycol (MeO-TEG-OBu)) combinations, where “insol” means aprecipitate was observed; “sol” means no precipitate was observed.Reactions were worked up with the addition of water and the organiclayer analyzed by GC coupled with mass spectrometry (GC/MS). GC/MSconversions for the same solvent/catalyst combinations are provided inTable 3.

TABLE 2 DIPEA Bu₃N (TBA) NMM Imid Acetone insol sol insol sol MeCN solsol insol sol MeO-DEG-OBu insol sol insol insol MeO-TEG-OBu insol solinsol insol

TABLE 3 Acetone MeCN MeO-DEG-OBu MeO-TEG-OBu DIPEA 83.3 94.3 91.9 92.9TEA 86.0 89.3 74.89 79.4 NMM 80.0 70.7 75.4 87.3 Imid 78.0 61.1 83.383.2

From Tables 2 and 3, the preferred combination was determined to beacetonitrile and DIPEA (diisopropylethylamine).

FIG. 2 provides graphs of reaction yield (as determined by GC) for thedifferent solvent and base catalyst combinations for reaction of2,2,2-trifluoroethanol with methyl chloroformate. The results shown inFIG. 2 indicate that a wide variety of solvents and catalysts can beutilized in this process.

Example 2. Solvent and Catalyst Evaluation for Continuous Flow Reactionof 2,2,2-Trifluoroethanol with CDI

Uncatalyzed TFE formation—Comparison.

Solutions of 2,2,2-trifluoroethanol (TFE) in DMF (4 M concentration) andCDI (1 M) were prepared. These solutions were injected into a SYRRISflow reactor system at a 2:1 molar ratio of alcohol to CDI at variousreaction temperatures and residence times. The ratio of intermediateproduct in which only one imidazole is displaced by the TFE(TFE-O—C(O)-Imid) to desired product (bis-trifluoroethyl carbonate) wasanalyzed by GC/MS. Although formation of the desired product went upwith temp and time, there was still a poor overall conversion (about 5to 43%). Similar experiments were run with DMSO and with DMF using 2.1and 2.2. equivalents of TFE relative to CDI, which did not show anysignificant improvement in conversion.

Catalyzed TFE Formation.

Solutions of 2,2,2-trifluoroethanol (TFE) in DMF or acetonitrile (1 or 2M containing 5 mol % DIPEA catalyst) and CDI (1 M in DMF or 0.5 M inacetonitrile) were prepared.

Reactions of TFE (1 M with 5 mol % DIPEA) and CDI (0.5 M) inacetonitrile; or TFE (2 M with 5 mol % DIPEA) and CDI (1 M) in DMF in aSYRRIS flow reactor system at a 2:1 molar ratio of alcohol to CDI atvarious reaction temperatures and a 2-minute residence time showedenhanced reactivity. The ratio of intermediate (TFE-O—C(O)-Imid) todesired product (F-DEC) was analyzed by GC/MS. All conditions gavesubstantially complete reaction as shown in Table 4. In Table 4, “Int.”refers to the intermediate TFE-O—C(O)-Imid formed by displacement of oneimidazole from CDI by TFE.

Reactions of TFE in DMF (2M with 5 mol % DIPEA) with pre-preparedTFE-O—C(O)-Imid (1 or 2 M) in DMF showed similarly enhanced reactivitywith the catalyst present.

TABLE 4 Mol Ratio F-DEC * Int. *. Solution A Solution B % Conv TFE:CDITemp ° C. 1 78.48 21.52 2M TFE/MeCN 0.5M CDI 78.48 1.8 100 2 81.21 18.792M TFE/MeCN 0.5M CDI 81.21 2.0 100 3 85.02 14.98 2M TFE/MeCN 0.5M CDI85.02 2.2 100 4 87.16 12.84 2M TFE/MeCN 0.5M CDI 87.16 2.4 100 5 89.7110.29 2M TFE/MeCN 0.5M CDI 89.71 2.6 100 6 78.84 21.17 2M TFE/MeCN 0.5MCDI 78.83 1.8 120 7 81.67 18.34 2M TFE/MeCN 0.5M CDI 81.66 2.0 120 885.48 14.52 2M TFE/MeCN 0.5M CDI 85.48 2.2 120 9 84.93 15.07 2M TFE/MeCN0.5M CDI 84.93 2.4 120 10 89.02 10.98 2M TFE/MeCN 0.5M CDI 89.02 2.6 12011 78.29 21.71 2M TFE/MeCN 0.5M CDI 78.29 1.8 140 12 84.99 15.01 2MTFE/MeCN 0.5M CDI 84.99 2.0 140 13 85.27 14.73 2M TFE/MeCN 0.5M CDI85.27 2.2 140 14 87.61 12.39 2M TFE/MeCN 0.5M CDI 87.61 2.4 140 15 90.159.85 2M TFE/MeCN 0.5M CDI 90.15 2.6 140 16 84.12 15.88 2M TFE/MeCN 0.5MCDI 84.12 1.8 160 17 84.26 15.74 2M TFE/MeCN 0.5M CDI 84.26 2.0 160 1886.41 13.59 2M TFE/MeCN 0.5M CDI 86.41 2.2 160 19 90.02 9.98 2M TFE/MeCN0.5M CDI 90.02 2.4 160 20 90.98 9.01 2M TFE/MeCN 0.5M CDI 90.99 2.6160 * = GC area under curve/10000

FIG. 3 provides a graph of % conversion (vertical axis) versus residencetime and temperature for reaction of 2,2,2-trifluoroethanol with DCI attemperatures from 60 to 120° C. (horizontal axis). The results shown inFIG. 3 indicate that conversion increases with both temperature andresidence time.

FIG. 4 provides a graph of % conversion (vertical axis) versustemperature (horizontal axis) and number of equivalents of2,2,2-trifluoroethanol relative to CDI for reaction of2,2,2-trifluoroethanol with DCI (from 1.8 to 2.6 equivalents) at2-minute reaction time from the data in Table 4. The results in FIG. 4and Table 4 indicate that conversion also increases with increasingnumber of equivalents of the alcohol, in addition to reactiontemperature.

Example 3. Solvent and Catalyst Evaluation for Continuous Flow Reactionof 3,3,3-Trifluoropropylene Oxide with Carbon Dioxide General BatchReaction Screening Procedure:

3,3,3-trifluoropropylene oxide (0.4 mL) and catalyst (10 mol %) werecombined with acetonitrile or optionally another solvent (1 mL) in atest tube. The test tube was flushed with CO₂ gas either from a gascylinder or from the addition of small chips of dry ice. The test tubewas capped with a balloon and the reaction was stirred under about 1 atmof CO₂ for 24 hours. The mixture was then analyzed by gas chromatographycouples with a mass spectrometry detector (GC/MS).

Alternate Batch Screening Procedure for Salt-Based Catalysts:

3,3,3-trifluoropropylene oxide (0.4 mL) and catalyst (10 mol %) werecombined with acetonitrile (1 mL) in a 10 mL thick-walled reaction tubewith a KONTES valve. The mixture was cooled in a −20° C. bath and dryCO₂ gas was purged into the tube for 30 seconds and sealed. The KONTESvalve was closed and the reaction was stirred under this mild pressureof CO₂ for 24 hours at room temperature. The mixture was then analyzedby GC/MS.

Discussion of Screening Experiments:

FIG. 5 provides a graph of % conversion (vertical axis) versus differentDBU-based catalysts (horizontal axis) for reaction of3,3,3-trifluoroproylene oxide with carbon dioxide in acetonitrilesolvent in the flow reactor experiments. The catalysts evaluated were A:DBU-acetic acid salt, B: DBU-lactic acid salt, C: DBU-hydrobromide salt,D: DBU-hydrochloride salt, E: DBU-propionic acid salt, F:1N-(2-hydroxyethyl)-DBU bromide salt, and G: 1N-ethyl-DBU bromide salt.

FIG. 6 provides a graph of % conversion (vertical axis) versus differenttetrabutylammonium (TBA)-based catalysts (horizontal axis) for reactionof 3,3,3-trifluoroproylene oxide with carbon dioxide in acetonitrilesolvent. The catalysts evaluated were A: tetrabutylammonium chloride, B:tetrabutylammonium iodide, C: tetrabutylammonium bromide, D:tetrabutylammonium hydrosulfate, E: tetrabutylammonium acetate, F:tetrabutylammonium fluoride, and G: tetrabutylammonium phosphate.

The results in FIG. 5 and FIG. 6 indicate that catalysts with chloride,bromide, and iodide anions outperformed all other anions. Mildlynucleophilic anions performed less well, and poorly nucleophilic anionseither performed poorly or not at all.

FIG. 7 provides a graph of % conversion versus different solvents(horizontal axis) for reaction of 3,3,3-trifluoroproylene oxide withcarbon dioxide in acetonitrile solvent with tetrabutylammonium bromide(TBAB) catalyst. The results in FIG. 7 indicate that using TBAB, thereis very little solvent effect with the exception of ethyl acetate (EA),which performed poorly.

Corning Flow Reactor Screening Tests:

3,3,3-Trifluoropropylene oxide (15 g) and catalyst (10 mol %) werecombined with acetonitrile (45 mL) and pumped through a CORNING AFRreactor. The liquid flow rate was set to 5.00 mL/min, and the gas flowof CO₂ was set to 10.00 mL/min by a mass flow controller. The reactiontemperature was set to 75° C. A back-pressure regulator was set to 2.5bar. The outlet of the reactor was diverted back into the feedstock,allowing for the solution to flow through the reactor multiple times, sothat a continuous loop was set up. Both due to reaction kinetics (slow)and ability to match the low mass flow rate of CO₂ to the higher rate ofliquid flow, the solution was run through the reactor several times,simulating a longer, higher volume reactor tube. For the small reactorbeing used, the CO₂ would cause too many bubble/foaming on the outlet ifthe rate was set too high. Dropping the gas flow rate allowed smootherflow. This lower gas flow rate did, however, lead to lower conversion,which was the primary reason to recycle the solution. Finally, TBABcatalyst can discolor at higher temperatures, so it was desirable tokeep the temperature relatively low. The solution was sampled for GC/MSanalysis periodically. The results generally agree with small-scaletesting, where catalysts with halide anions were most active. Moreeffect of the cation was observed, showing that tetraalkylammonium waspreferred, and tetrabutylammonium was most preferred.

FIG. 8 provides graphs of % conversion versus residence time fordifferent catalysts for reaction of 3,3,3-trifluoroproylene oxide withcarbon dioxide in acetonitrile solvent in the flow reactor. The resultsin FIG. 8 indicate that the larger scale CORNING AFR flow reactor testsclosely match the batch and small-scale flow reaction screening tests.The catalysts preferably have a halide anion and tetrabutylammoniumcation.

Example 4. Continuous Flow Reaction Preparation of 2,2,2-TrifluoroethylMethyl Carbonate (TFEMC)

A mixture of 2,2,2-trifluoroethanol (125.12 g) and DIPEA (177.76 g, 1.1eq) was prepared. A solution of methyl chloroformate (142.87 g, “MCF”,3.25 eq) in acetonitrile (170.82 g) was prepared. The solutions wereboth pumped at 1.00 mL/min into the CORNING AFR reactor with a 2.7 mLvolume flow reactor plate held at 50° C. Water was pumped at 1 mL/mininto a second reaction plate attached to the outlet of the first plateto mix with the eluent of the first reactor plate and quench anyremaining MCF. After several minutes, the flow rate of the MCF solutionwas lowered to 0.915 mL/min to minimize bubble formation out of thereactor system due to excess MCF. The entire collected eluent wastitrated with 4N HCl to a yellow color. The layers were then separated.The product layer was washed with 10% HCl (2×20 mL), then brine (20 mL).The organic phase was then dried over anhydrous MgSO4. GC/MS showed97.1% purity for the TFEMC product. The liquid was distilled through anOldershaw distillation column to remove solvent and purify the TFEMC.Re-distillation of off-fractions provided 136 g of pure TFEMC (69%yield, GC/MS purity >99.9%).

Example 5. Continuous Flow Reaction Preparation ofBis(2,2,2-Trifluoroethyl) Carbonate (F-DEC)

A solution of 2,2,2-trifluoroethanol (50.19 g) and DIPEA (3.31 g, 0.05equivalents) in acetonitrile (solution made to 300 mL total volume) wasprepared. A second solution of CDI (39.71 g, 0.49 equivalents) inacetonitrile (solution made to 600 mL total volume) was prepared. Thefirst and second solutions were pumped into a 1 mL coil reactor held at80° C. in a themostated oil bath at a rate of 1 mL/min and 2 mL/min,respectively. After about 50 mL of effluent had eluted, the remainingeffluent was collected in a single main batch and analyzed. Aftercollection, the liquid was distilled through an Oldershaw distillationcolumn to remove acetonitrile, then to collect the pure product.

Example 6. Continuous Flow Reaction Preparation ofTrifluoromethylpropylene Carbonate (TFPC)

A 500 mL 3-neck round bottom flask was charged with3,3,3-trifluoropropylene oxide (100.86 g), TBAB catalyst (14.5970 g, 5mol %), and acetonitrile (200 mL). The resulting mixture wasmagnetically stirred to dissolve the TBAB, and was then pumped through aCORNING AFR reactor at a rate of 5.5 mL/min, with a CO₂ gas flow rate of23 mL/min (initial). The gas flow rate was adjusted as the reactionprogressed to prevent large amounts of foaming and bubble formation fromthe outlet. The reaction temperature was set to 65° C. After one hour,the liquid flow rate was increased to 6.0 mL/min. The reactor output wasput back into the round bottom flask, allowing the solution to circulatethrough the reactor system repeatedly. After 24 hours, an additionalcharge of TBAB (7.2050 g) was added to the flask and the reactiontemperature was increased to 75° C. After 48 hours total reaction time,the reaction had progressed to 93% completion and elution was stopped.This eluent was combined with other small scale runs and distilledthrough a 5 plate Oldershaw column, first at 1 atm to removeacetonitrile and residual 3,3,3-trifluoropropylene oxide, then graduallyreducing pressure to 0.6 Torr to distill the TFPC from the catalyst toprovide 288 g (54% yield) of TFPC (GC purity >99.5%). Additionalfractions were kept for further purification.

All references, including publications, patent applications, andpatents, cited herein are hereby incorporated by reference to the sameextent as if each reference were individually and specifically indicatedto be incorporated by reference and were set forth in its entiretyherein.

The use of the terms “a” and “an” and “the” and similar referents in thecontext of describing the invention (especially in the context of thefollowing claims) are to be construed to cover both the singular and theplural, unless otherwise indicated herein or clearly contradicted bycontext. The terms “comprising,” “having,” “including,” and “containing”are to be construed as open-ended terms (i.e., meaning “including, butnot limited to,”) unless otherwise noted. The terms “consisting of” and“consists of” are to be construed as closed terms, which limit anycompositions or methods to the specified components or steps,respectively, that are listed in a given claim or portion of thespecification. In addition, and because of its open nature, the term“comprising” broadly encompasses compositions and methods that “consistessentially of” or “consist of” specified components or steps, inaddition to compositions and methods that include other components orsteps beyond those listed in the given claim or portion of thespecification. Recitation of ranges of values herein are merely intendedto serve as a shorthand method of referring individually to eachseparate value falling within the range, unless otherwise indicatedherein, and each separate value is incorporated into the specificationas if it were individually recited herein. All numerical values obtainedby measurement (e.g., weight, concentration, physical dimensions,removal rates, flow rates, and the like) are not to be construed asabsolutely precise numbers, and should be considered to encompass valueswithin the known limits of the measurement techniques commonly used inthe art, regardless of whether or not the term “about” is explicitlystated. All methods described herein can be performed in any suitableorder unless otherwise indicated herein or otherwise clearlycontradicted by context. The use of any and all examples, or exemplarylanguage (e.g., “such as”) provided herein, is intended merely to betterilluminate certain aspects of the invention and does not pose alimitation on the scope of the invention unless otherwise claimed. Nolanguage in the specification should be construed as indicating anynon-claimed element as essential to the practice of the invention.

Preferred embodiments of this invention are described herein, includingthe best mode known to the inventors for carrying out the invention.Variations of those preferred embodiments may become apparent to thoseof ordinary skill in the art upon reading the foregoing description. Theinventors expect skilled artisans to employ such variations asappropriate, and the inventors intend for the invention to be practicedotherwise than as specifically described herein. Accordingly, thisinvention includes all modifications and equivalents of the subjectmatter recited in the claims appended hereto as permitted by applicablelaw. Moreover, any combination of the above-described elements in allpossible variations thereof is encompassed by the invention unlessotherwise indicated herein or otherwise clearly contradicted by context.

The embodiments of the invention in which an exclusive property orprivilege is claimed are defined as follows:
 1. A continuous process forpreparing organic carbonate solvent of Formula (I):

comprising the steps of: (a) contacting a first reactant with a reactivecarbonyl source in reaction stream containing a catalyst flowing througha continuous flow reactor at a temperature in the range of about 20° C.to about 160° C., and at a flow rate providing a residence time in therange of about 0.1 minute to about 24 hours; (b) optionally quenchingany remaining reactive carbonyl source; (c) collecting a reactoreffluent exiting from the continuous flow reactor; (d) recovering acrude product from the reactor effluent; and (e) purifying the crudeproduct to obtain the organic carbonate compound of Formula (I);wherein: the reactive carbonyl source is carbon dioxide; and the firstreactant is an epoxide of Formula (III):

the catalyst comprises at least one material selected from the groupconsisting of a bicyclic amidine, an acid addition salt of aphosphazene, an acid addition salt of a bicyclic guanidine, a quaternaryammonium halide, and a quaternary phosphonium halide; Z is a covalentbond; x is 1; R and R¹ are the same and are selected from the groupconsisting of (a) C₁-C₆ alkyl and (b) C₁-C₆ fluoroalkyl comprising atleast one fluoro substituent; R² is H; R³ and R⁴ both are CH and aredirectly connected by the covalent bond Z.
 2. The process of claim 1,wherein the reaction stream further comprises an aprotic organic solventin which the first reactant, the carbonyl source, and the catalyst aredissolved.
 3. The process of claim 2, wherein the aprotic organicsolvent comprises at least one material selected from the groupconsisting of an ether, a nitrile, an ester, an organic carbonate ester,an amide, a ketone, a sulfone, a sulfoxide, a hydrocarbon, a halogenatedhydrocarbon, and a phosphoramide.
 4. The process of claim 2, wherein theaprotic organic solvent is selected from the group consisting of anitrile, an ester, an organic carbonate ester, an amide, a ketone, asulfone, a sulfoxide, and a halogenated hydrocarbon.
 5. The process ofclaim 2, wherein the aprotic organic solvent comprises acetonitrile. 6.The process of claim 2, wherein the epoxide is dissolved in the aproticorganic solvent at a concentration of about 0.5 to about 6 molar (M). 7.The process of claim 1, wherein R and R¹ are C₁ to C₄ alkyl.
 8. Theprocess of claim 1, wherein R and R¹ are C₁ to C₄ fluoroalkyl comprisingat least one fluoro substituent.
 9. The process of claim 1, wherein thecatalyst is present in the reaction stream at a concentration of about 1to 20 mol % relative to the epoxide.
 10. The process of claim 9, whereinthe catalyst is present at a concentration of about 1 to about 15 mol %relative to the epoxide.
 11. The process of claim 1, wherein the carbondioxide is present in the reaction stream at a pressure in the range ofabout 1 to about 10 bar.
 12. The process of claim 1, wherein thereaction stream flowing through the continuous flow reactor is heated instep (a) at a temperature in the range of about 50° C. to about 120° C.13. The process of claim 1, wherein the catalyst is selected from thegroup consisting of tetrabutylammonium bromide, tetrabutylammoniumchloride, tetrabutylammonium iodide, and benzyltriethylammonium bromide.14. The process of claim 1, wherein the epoxide is3,3,3,-trifluoropropylene-1,2-oxide.
 15. The process of claim 1, whereinthe compound of Formula (I) is purified in step (e) by distillation. 16.The process of claim 1, wherein the epoxide is dissolved in an aproticorganic solvent at a concentration of about 0.5 to about 6 molar (M);the catalyst is selected from the group consisting of tetrabutylammoniumbromide, tetrabutylammonium chloride, tetrabutylammonium iodide, andbenzyltriethylammonium bromide; the catalyst is present in the reactionstream at a concentration of about 1 to about 15 mol % relative to theepoxide; the carbon dioxide is present in the reaction stream at apressure in the range of about 1 to about 10 bar; and the continuousflow reactor is heated in step (a) at a temperature in the range ofabout 50° C. to about 120° C.
 17. The process of claim 16, wherein theaprotic organic solvent is selected from the group consisting of anitrile, an ester, an organic carbonate ester, an amide, a ketone, asulfone, a sulfoxide, and a halogenated hydrocarbon.
 18. The process ofclaim 16, wherein the aprotic organic solvent is acetonitrile.
 19. Theprocess of claim 16, wherein the epoxide is3,3,3,-trifluoropropylene-1,2-oxide.